Steroid Withdrawal in Pediatric Kidney Transplant Allows Better Growth, Lipids and Body Composition: A Randomized Controlled Trial

Abstract

Background: Glucocorticoid immunosuppressant therapy in pediatric kidney transplant (Tx) recipients does not allow the improvement of growth after Tx. Objective: To determine the effect of early steroid withdrawal (SW) on longitudinal growth, insulin sensitivity (IS), and body composition (BC). Methods: This was a prospective, randomized, multicenter study in Tx. Insulin-like growth factor (IGF)-I, IGF-binding protein 3 (IGFBP3), IS, and BC (DEXA/pQCT) were determined at baseline and up to 12 months after Tx. Results: A total of 30 patients were examined; 14 patients were assigned to the SW group (7 male, 7 female; 12 in Tanner stage I) and 16 patients were assigned to the steroid control (SC) group (10 male, 6 female;12 in Tanner stage I). Their chronological age was 7.8 ± 4.3 years, height was -2.3 ± 0.99 SD scores (SDS), and body mass index -0.3 ± 1.2 SDS. After 1 year, the SW group showed an increase in height SDS (+1.2 ± 0.22 vs. +0.60 ± 0.13 SDS in the SC group, p < 0.02), lower IGFBP3 (p < 0.05), cholesterol (p < 0.05), and higher high-density lipoprotein cholesterol (p < 0.05). SW patients had lower trunk fat with no differences in IS. Only in prepubertal patients, the SW group had lower glycemia (p < 0.05), very low-density lipoprotein cholesterol (p < 0.01), triglycerides (p < 0.05), triglycerides/glycemia index (TyG; p < 0.02), and better lean mass. Both groups showed an improvement in lean mass after kidney Tx. Conclusions: SW improved longitudinal growth, lipid profile, and trunk and lean fat in Tx patients. In prepubertal recipients, the decrease in TyG suggests better IS.

Immunosuppressive therapy for kidney transplantation in children and adolescents: systematic review and economic evaluation

“…8 However, post transplant, the steroidal therapy often included in immunosuppression regimens can affect longitudinal growth and calcium/ phosphorous metabolism. 9,10 Aetiology, pathology and prognosis…”

Clinical Significance of Peripheral Blood Lymphocyte Sensitivity to Glucocorticoids for the Differentiation of High-risk Patients With Decreased Allograft Function After Glucocorticoid Withdrawal in Renal Transplantation

“…[1][2][3][4] Glucocorticoid reduction/withdrawal is one of the most important issues for successful long-term immunosuppressive therapy in renal transplantation. [5][6][7][8] However, glucocorticoids need to be restarted to prevent the worsening of renal function because of occurrence of acute rejection episodes in some patients or in patients who experience glucocorticoid withdrawal syndrome. [9][10][11] Increasing the dose of the immunosuppressive drugs could also result in a variety of side effects that plague the patients.…”

Long-term nutritional and cognitive outcomes after liver transplantation in childhood

“…This study, using DXA to examine bone mineral density after transplantation, reported no change in lean mass in 9 children at 6 months after transplant 72 . In contrast, lean mass and fat mass both increased at 12 months after renal transplantation in 30 children; with greater total body and trunk fat in those who remained on steroids compared to those who stopped steroids after 6 days 67 . Improvement in fat free mass, but no change in fat mass was noted on longitudinal DXA scanning in 41 children at 24 months after lung transplantation 73 .…”

“…The role of immunosuppression in the development of obesity was proposed in an editorial in 2008 discussing whether children after liver transplant were more prone to non-alcoholic fatty liver disease 119 . Several studies have implicated steroids as the cause for reduced body cell mass and increased fat mass after renal transplantation 66,67 . The use of steroids immediately post-transplant is almost universal for all solid organs and by all centres.…”

“…Body composition changes after transplantation are not well defined. Increased fat mass and reduced lean mass have been reported in both adults and children in the first two years after renal transplantation; with early steroid withdrawal a significant factor in fat accretion and reduced lean mass recovery 66,67 .…”